(3R,4R,5S)-4,5-Diamino-3-hydroxy-cyclohex-1-enecarboxylic acid derivatives of formula I, especially the (3R,4R,5S)-5-amino-4-acetylamino-3-(1-ethyl-propoxy)-cyclohex-1-ene-carboxylic acid ethyl ester and its pharmaceutically acceptable additional salts are potent inhibitors of viral neuraminidase (J. C. Rohloff et al., J. Org. Chem. 63, 1998, 45454550; WO 98/07685). Improvements to Rohloff s process have been reported. (M. Federspiel et al., Org. Proc. Res. Dev. 1999 3(4): 266-274, P. J. Harrington et al., Org. Proc. Res. Dev. 2004 8(1): 86-91) Alternatively, oseltamivir can be prepared as disclosed by S. Albrecht et al. in EP 1 127 872 published Aug. 29, 2001. New approaches for the preparation of oseltamivir have been reviewed. (M. Shibasaki and M. Kamai, Eur. J. Org. Chem. 2008 1839-1850).
There is a continuing need for improved processes to prepare oseltamivir phosphate and related derivatives of (3R,4R,5S)-4,5-diamino-3-hydroxy-cyclohex-1-enecarboxylic acid. Shikimic acid (II) [(3R,4S,5R)-3,4,5-trihydroxy-cyclohex-1-enecarboxylic acid], which can be easily obtained from biotechnological processes, e.g. genetic engineering, fermentation (Sunil S. Chandran, Jian Yi, K. M. Draths, Ralph von Daeniken, Wolfgang Weber, and J. W. Frost, Biotechnologie Progress, Vol. 19, No. 3, 2003, 808-814) is a convenient starting material. The present invention provides a new process for preparing Oseltamivir and related derivatives in good quality and yield from shikimic acid.